Antisense antiviral compound and method for treating arenavirus infection
First Claim
1. A method of inhibiting viral infection in mammalian cells by an Arenavirus in the Arenaviridae family, comprising(a) exposing the cells to an antisense oligonucleotide compound composed of morpholino subunits and phosphorus-containing intersubunit linkages joining a morpholino nitrogen of one subunit to a 5′
- exocyclic carbon of an adjacent subunit, and characterized by;
(i) a substantially uncharged, nuclease-resistant backbone,(ii) capable of uptake by mammalian host cells,(iii) containing between 12-40 nucleotide bases,(iv) having a targeting sequence of at least 12 contiguous subunits complementary to SEQ ID NO;
1, and(v) conjugated to the oligonucleotide, an arginine-rich polypeptide effective to promote uptake of the compound into infected host cells, and(b) by said exposing, forming a heteroduplex structure (i) composed of the virus'"'"' vRNA or vcRNA strand and the oligonucleotide compound, and (ii) characterized by a Tm of dissociation of at least 45°
C.
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Abstract
The invention provides antisense antiviral compounds and methods of their use and production in inhibition of growth of viruses of the Arenaviridae family and in the treatment of a viral infection. The compounds are particularly useful in the treatment of Arenavirus infection in a mammal. The antisense antiviral compounds are substantially uncharged morpholino oligonucleotides have a sequence of 12-40 subunits, including at least 12 subunits having a targeting sequence that is complementary to a region associated with viral RNA sequences within a 19 nucleotide region of the 5′-terminal regions of the viral RNA, viral complementary RNA and/or mRNA identified by SEQ ID NO:1.
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Citations
8 Claims
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1. A method of inhibiting viral infection in mammalian cells by an Arenavirus in the Arenaviridae family, comprising
(a) exposing the cells to an antisense oligonucleotide compound composed of morpholino subunits and phosphorus-containing intersubunit linkages joining a morpholino nitrogen of one subunit to a 5′ - exocyclic carbon of an adjacent subunit, and characterized by;
(i) a substantially uncharged, nuclease-resistant backbone, (ii) capable of uptake by mammalian host cells, (iii) containing between 12-40 nucleotide bases, (iv) having a targeting sequence of at least 12 contiguous subunits complementary to SEQ ID NO;
1, and(v) conjugated to the oligonucleotide, an arginine-rich polypeptide effective to promote uptake of the compound into infected host cells, and (b) by said exposing, forming a heteroduplex structure (i) composed of the virus'"'"' vRNA or vcRNA strand and the oligonucleotide compound, and (ii) characterized by a Tm of dissociation of at least 45°
C. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8)
- exocyclic carbon of an adjacent subunit, and characterized by;
Specification